Acyloins or α-hydroxyketones (and -aldehydes) are important functional units in many biologically active substances. In addition, they are important synthetic intermediates and their small bifunctional unit is important as a site for double coupling with other synthetic building blocks, e.g. in heterocyclic chemistry.
The same applies to derivatives of acyloins, in particular those in which the hydroxy group is esterified or otherwise protected or derivatized. Acyloins with an unprotected hydroxy group are also designated as free acyloins. The keto- (or aldehyde) groups can most importantly be derivatized by acetal formation, condensation, e.g. to imines, etc., or alkenylation, e.g. by reactions of the Wittig type.
It is a common property of all α-monosubstituted acyloins and their derivatives that they have a chiral centre on the α-(OH)-Carbon atom, i.e. in the α-hydroxy position, and this can easily be racemized by the neighbouring keto group. In many acyloins, especially in free acyloins (PG=H), there can also be an acyloin shift, which is an exchange of keto and hydroxy group through an intermediate with the dihydroxyalkene structure. This, happens preferably with basic catalysis.
In the context of the present invention, an asymmetrically substituted acyloin is designated as an acyloin which bears different substituents R1 and R2 on the keto group and on the α-hydroxymethylene group, in other words, those compounds which form an acyloin of another structure as a result of an acyloin shift. The nomenclature of the substituents is always in relation to the standard formula, not the shift version with exchanged keto and alcohol functions, which is only depicted here for the purposes of demonstration. 
The preferred synthetic procedure for acyloins is by acyloin condensation from carboxylic acid derivatives or aldehydes, which is a procedure which is especially suitable for symmetrical acyloins. Other procedures employ the oxidation of 1,2-diols and the reduction of 1,2-dioxo compounds. The latter methods have also been performed asymetrically and enzymatically (see e.g., Bioorg. Chemistry 21, 1993, 342; Bull. Chem. Soc. Jpn. 1994, 3314; J. Chem. Soc., Perkin Trans I1991, 1329, ibid. 1996, 425; J. Chem. Soc., Chem. Commun. 1993; 341, J. Org. Chem. 51, 1986, 25-36; ibid. 1997, 1854). All the methods mentioned above have in common that they cannot or can only with difficulty be used for the specific synthesis of asymetric acyloins, since cross-coupling and regioselective redox reactions are often difficult to control or to perform on a large scale (cofactors).
Acyloins and their derivatives, especially those with an allyl substituent as group R2— that is homoallylacyloins (homoallylalcohols)- and with a methyl group as the preferred residue R1, are also excellent building blocks for the synthesis of epothilones, where the acyloin unit is mainly found as carbon atoms C15 and C16, in accordance with the epothilone numbering system given below.
Epothilones are naturally occurring substances with extraordinary biological activity, for example as mitosis inhibitors, compounds which affect microtubular activity, cytotoxic agents and fungicides. In particular, they possess paclitaxel-like properties and even surpass the activity of paclitaxel (Taxol®) in some tests. They are now being examined in clinical studies on the treatment of cancer. 
Epothilone, in particular epothilones B and D, possess a C7-C18(methyl) unit in the “north moiety”, which corresponds to a modified polyprenyl- (polyisoprene-) chain, and can for example be synthesized in accordance with the German Patent Applications No. 197 13 970.1 and No. 100 51 136.8. There is also a C1-C6 (methyl) unit in the “south moiety”, which can be synthesized by aldole type reactions, e.g. in accordance with German Patent Application No. 197 01 758.4, (1998).
The terms structural element, synthetic building block and building block, are used as synonyms in the context of the present invention. The numbering of the epothilone components is as with the epothilones (see above). In particular, substituents, especially methyl branches, are usually not mentioned separately when defining the structural elements as a C(number)-C(number) region, but are expressly included, although this is not obligatory.
Up to now, allyl compounds, including prenyl derivatives, have usually been synthesized for the production of the structural element C7-C21 of the epothilones or of subunits, especially C7-C15/16 and C11-C15/16 structural units, where the allyl compounds were coupled with C15-C16 methyl structural units which were difficult to access or in the wrong oxidation state.
Racemates are usually produced in the method for the production of the epothilone north moiety, in which the oxidation state at C15 and C16 is correct for epothilone synthesis, in particular, in accordance with German Patent Application 100 51 136.8. Therefore, all known methods for the synthesis of the epothilone north moiety exhibit the disadvantage that an asymmetric synthesis can only be performed with difficulty.
α-Hydroxyketones with at least one chiral centre on the α-hydroxy position are therefore important precursors of biologically active substances, such as polyketides and terpenoids and, in particular, epothilones and their derivatives. An economic production method is therefore of great significance.
An optimal and economic, possibly enzymatically catalyzed, production of acyloins which are not racemic at the α-hydroxy position should advantageously fulfil a series of conditions, such as for example high enantioselectivity, relative to the α-hydroxy position of the acyloin, high selectivity for diastereomers, good yield in space and time (short reaction times, high degree of conversion of the enantiomer, high educt and product concentrations), low substrate specificity for the enzyme, high chemical yield of the desired product, low quantities of catalysts (especially of enzymes), easy purification of the synthetic products, good solubility of educt and product under the reaction conditions and cheap synthesis, i.e. easily synthesizable educts, easy handling of the educts, reagents and enzymes.
As already mentioned above, structural elements C7-C16-Me of the epothilones or their subunits, in particular C7-C15 structural components, have up to now been synthesized with prenyl derivatives from nucleophilic prenyl metal derivatives, e.g. in accordance with the method disclosed in German Patent Application No. 197 13 970.1. Although this method exhibits clear advantages in comparison with other methods for the assembly of this structural element, it has the disadvantage that prenyl metal species, especially of barium, must be produced. This is expensive, tedious and leads to side-products during the reaction, e.g., from allyl shift (SN2′ substitution) during the reaction. Oxidation on C15 or C16 is also necessary to introduce the oxygen function, or this function must be included in a suitable manner, which sets difficult requirements for the building blocks and often brings with it problems for later synthetic steps.
In accordance with the methods known from the art, there was often a problem in the coupling to C7 with the structural element C1-C6-Me. This should occur with syn-specificity. Previously known procedures mostly use enolates produced with base; side reactions due to these reagents are possible and/or the partners can only be coupled correctly and with an adequate yield with the help of special protecting groups or through a suitable influence of the stereocenter on C3.